Regulation of syndecan-4 phosphorylation in vivo

J Biol Chem. 1998 May 1;273(18):10914-8. doi: 10.1074/jbc.273.18.10914.


Recent studies suggest that some of the heparan sulfate-carrying proteoglycans may directly participate in signaling via their cytoplasmic tail. The present investigation addresses the potential involvement of syndecan-4, a widely expressed transmembrane proteoglycan, in this process. We found that the cytoplasmic tail of syndecan-4 is phosphorylated on a single serine residue (Ser183) in growth-arrested NIH 3T3 fibroblasts, with a stoichiometry of 0.3 mol Pi/mol syndecan-4. Treatment of the cells with a protein kinase C (PKC)-activating phorbol ester lead to a 2.5-fold increase in Ser183 phosphorylation. This increase was inhibited by a generic PKC inhibitor but not by an inhibitor specific to the calcium-dependent conventional PKCs, suggesting that the cytoplasmic tail of syndecan-4 is phosphorylated by a calcium-independent novel PKC isozyme. Application of 10-30 ng/ml basic fibroblast growth factor (bFGF) produced a 2-3-fold reduction in the phosphorylation of syndecan-4. Because treatment with the phosphatase inhibitor calyculin prevented the bFGF-induced decrease in syndecan-4 phosphorylation, the effect of bFGF appears to be mediated by a protein serine/threonine phosphatase type 1 or 2A. We conclude that the cytoplasmic tail of syndecan-4 is subject to in vivo phosphorylation on Ser183, which is regulated by the activities of a novel PKC isozyme and a bFGF-dependent serine/threonine phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Alkaloids
  • Amino Acid Sequence
  • Animals
  • Benzophenanthridines
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factor 2 / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Phenanthridines / pharmacology
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Proteoglycans / metabolism*
  • Syndecan-4


  • Alkaloids
  • Benzophenanthridines
  • Enzyme Inhibitors
  • Membrane Glycoproteins
  • Phenanthridines
  • Proteoglycans
  • Sdc4 protein, mouse
  • Syndecan-4
  • Fibroblast Growth Factor 2
  • chelerythrine
  • Protein Kinase C